This application is a competing renewal of the Dartmouth COBRE research program titled Dartmouth Lung Biology Center for Molecular, Cellular and Translational Research. The proposal builds on nine years of COBRE-funded, research that have supported the development of new concepts and innovative model systems for studying the underlying mechanisms of lung disease and chronic airway infection, bringing us closer .to our 'goal of developing new therapeutics for these diseases. Lung disease is the third most frequent cause of death in the United States, claiming ~360,000 Americans annually. Tragically, millions more live with chronic lung diseases including asthma, chronic obstructive pulmonary disease (COPD) and cystic fibrosis (CF), and the number of patients is increasing at an alarming rate. Thus, a better understanding of the etiology of lung disease is required, as are new therapeutic approaches. With support from COBRE I and II (2003-preserit), our Center has grown dramatically, from 6 investigators in 2002 to 32 tenure-track investigators in 2012. Of our 32 ;faculty, 12 are physician-scientists recruited to the Center with COBRE support. Our faculty have developed |novel in vitro models to study host-pathogen interactions in CF; initiated an ambitious program to characterize !the CF respiratory microbiome and mycobiome and .thus develop more effective therapies for chronic, polymicrobial lung infections; and established an ambitious CF drug-discovery program. During the period of COBRE l/ll support, our group has published 1,007 papers, garnering editorial and Faculty of 1000 recognition. Our faculty have also obtained $151M.in extramural research support and received national awards. Overall, with funding from COBRE l/ll we have developed an internationally recognized Center of Biomedical Research; |Excellence in Lung Biology with the overarching goals of elucidating the underlying mechanisms of chronic microbial infections of the lungs and developing new approaches to treat, these diseases. The goals of COBRE are to build upon our successes, establishing a free-standing Center arid developing paradigms directly relevant to CF and other major lung diseases, including COPD and asthma. This research will be supported by a Pilot Project Program and four Center-specific cores: (1) Education, Mentoring and Administration, (2) Host- , Pathogen Interaction, (3) Live-Cell Imaging and (4) Translational Research. In this section, we will describe . the Pilot Project Program (P3) and how it will support the Dartmouth Lung,Biolpgy Center (LBC).